Abstract
Mesial temporal lobe epilepsy (mTLE) is the most prevalent form of focal epilepsy, and hippocampal sclerosis (HS) is considered the most frequent associated pathological finding. Recent connectivity studies have shown that abnormalities, either structural or functional, are not confined to the affected hippocampus, but can be found in other connected structures within the same hemisphere, or even in the contralesional hemisphere. Despite the role of hippocampus in memory functions, most of these studies have explored network properties at resting state, and in some cases compared connectivity values with neuropsychological memory scores. Here, we measured magnetoencephalographic responses during verbal working memory (WM) encoding in left mTLE patients and controls, and compared their effective connectivity within a frontotemporal network using dynamic causal modelling. Bayesian model comparison indicated that the best model included bilateral, forward and backward connections, linking inferior temporal cortex (ITC), inferior frontal cortex (IFC), and the medial temporal lobe (MTL). Test for differences in effective connectivity revealed that patients exhibited decreased ipsilesional MTL-ITC backward connectivity, and increased bidirectional IFC-MTL connectivity in the contralesional hemisphere. Critically, a negative correlation was observed between these changes in patients, with decreases in ipsilesional coupling among temporal sources associated with increases contralesional frontotemporal interactions. Furthermore, contralesional frontotemporal interactions were inversely related to task performance and level of education. The results demonstrate that unilateral sclerosis induced local and remote changes in the dynamic organization of a distributed network supporting verbal WM. Crucially, pre-(peri) morbid factors (educational level) were reflected in both cognitive performance and (putative) compensatory changes in physiological coupling.
Highlights
The analysis of functional integration in the brain is useful to investigate normative cognitive processes, and provides an unique window into neurological and neuropsychiatric disorders, as their clinical impact is related to the integrity of distributed neural networks (Bassett et al, 2009; Buckholtz and Meyer-Lindenberg, 2012; Guye et al, 2008)
In this study we examined the impact of unilateral left hippocampal sclerosis on the reorganization of the functional architecture of the neural networks underlying verbal working memory (WM), and investigated whether this reorganization was influenced by relevant clinical and demographic factors
Using dynamic causal modelling (DCM) for event related responses, we first established that the best model involved a bilateral network comprising frontotemporal sources; such as inferior temporal cortex (ITC), inferior frontal cortex (IFC) and medial temporal lobe (MTL)
Summary
The analysis of functional integration in the brain is useful to investigate normative cognitive processes, and provides an unique window into neurological and neuropsychiatric disorders, as their clinical impact is related to the integrity of distributed neural networks (Bassett et al, 2009; Buckholtz and Meyer-Lindenberg, 2012; Guye et al, 2008). Hippocampal sclerosis is the most frequent pathological finding in patients with this form of epilepsy (Wieser, 2004). These studies have shown that connectivity abnormalities are not restricted to the pathological hippocampus, but can be observed in other connected structures within the same hemisphere, or even in the contralesional hemisphere. These findings have led to the notion of mTLE as a ‘network disease’ (Bonilha et al, 2012). Our focus on WM was motivated by previous neuropsychological studies demonstrating impaired WM in patients with
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